Antitumor response to recombinant murine interferon γ correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages

Paul L. Black, Hamblin Phillips, Henry R. Tribble, Robin Pennington, Mark schneider, James E. Talmadge

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The mechanism of therapeutic activity for recombinant murine interferon-γ(rMu IFNγ) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFNγ administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFNγ demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFNγ (2.5×106 U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.

Original languageEnglish (US)
Pages (from-to)299-306
Number of pages8
JournalCancer Immunology Immunotherapy
Volume37
Issue number5
DOIs
StatePublished - Sep 1 1993

Keywords

  • Antitumor response
  • Immunotherapy
  • Macrophages
  • Murine interferon γ
  • Organ-associated CTL

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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